内毒素对大鼠膈肌收缩功能及线粒体超微结构的影响  

The effect of endotoxins on the diaphragmatic contractile function and mitochondrial ultrastructure

作　　者：焦光宇[1] 毕涛[2] 高鸿美[3] 李承峰[1] 刘春利[1] 聂鑫[1] 谭书涛[1] 何平[1] 

机构地区：[1]中国医科大学附属盛京医院呼吸内科,沈阳110004 [2]沈阳医学院附属奉天医院检验科 [3]沈阳医学院附属奉天医院呼吸内科

出　　处：《中华结核和呼吸杂志》2008年第6期431-435,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：辽宁省科委博士启动基金资助项目（20021033）;沈阳市科委青年人才启动基金资助项目（2003-48）

摘　　要：目的观察内毒素（革兰阴性菌细胞壁的脂多糖成分）对大鼠膈肌收缩功能及线粒体超微结构的影响，为探索呼吸衰竭发生机制提供新思路。方法将28只SD大鼠按随机数字表法分为：（1）对照组（10只）气管内灌注生理盐水；（2）实验组气管内灌注内毒素，浓度为200μg／ml，剂量为0．5ml／kg，制备急性肺损伤（acute lung injury，ALI）动物模型，再分为观察4h（内毒素4h组，9只）及24h（内毒素24h组，9只）2组。然后，取膈肌肌条，用体外电生理方法测定膈肌的最大收缩力、颤搐收缩峰值及疲劳指数。另外取膈肌标本固定后做电镜检测。采用SPSS15．0统计软件分析数据，组间比较用单因素方差分析及q检验。计量资料以x^-±s表示。结果（1）内毒素4h组膈肌的收缩力及颤搐收缩峰值[（3．4±1．9）及（0．9±0．4）N／cm^2，经肌肉横截面积校正]均明显低于对照组[（6．7±4．3）及（2．2±1．7）N／cm^2，F值分别为3．59、3．78，P〈0．05]；内毒素24h组膈肌的收缩力及颤搐收缩峰值[（4．1±1．2）和（1．2±0．7）N／cm^2]较内毒素4h组明显恢复。（2）膈肌的疲劳指数在内毒素4h及24h组（分别为0．07±0．06和0、12±0．07）均较对照组（0．26±0．14）明显下降（F=9．27，P〈0．01）。（3）内毒素4h组及24h组电镜下显示膈肌间线粒体肿胀、嵴减少，外膜模糊、变形，部分溶解破坏等超微结构的改变。结论内毒素可导致ALI大鼠膈肌的收缩力下降并易于疲劳，这可能是导致呼吸功能衰竭的原因之一。Objective To investigate the diaphragmatic contractile function and mitochondrial ultrastructure in rats with acute lung injury. Methods Twenty-eight Sprague-Dawley （SD） rats were allocated randomly into three groups： a control group （ n = 10）, a lipopolysaccharide （ LPS, endotoxins） 4 h group （ n =9） and a LPS 24 h group （ n =9）. Diaphragmatic samples were taken at 4 h and 24 h after 100 μg/kg LPS was instilled into the trachea of the rats. Normal saline （0. 5 ml/kg） was instilled in the control group. Then the contractile function of the diaphragmatic samples, including the peak twitch tension, frequency depended force and fatigue index （FI）, was tested in vitro. The diaphragmatic ultrastructure was also measured by electron microscopy. SPSS version 15.0 was used for statistical analysis. Data were presented as x^-± s, and means were compared with analysis of variance. Results The diaphragmatic forcegenerating capacity and peak twitch tension in LPS 4 h group[ （3.4 ± 1.9） ; （0. 9 ±0. 4） N/cm^2 ] decreased significantly compared to the control group [ （ 6.7 ± 4. 3 ） ; （ 2.2 ± 1.7 ） N/cm^2, F = 3.59 and 3.78 respectively, P 〈0. 05], but a marked recovery was observed in LPS 24 h group[ （4. 1 ± 1.2） and （ 1.2 ± 0.7） N/cm^2） , P 〈0.05 ]. The FI was also reduced remarkably in LPS4 h and LPS24 h group （0.07 ± 0. 06 ;0. 12 ± 0. 07 ） compared to the control group （ 0. 26 ± 0. 14, F =9.27, P 〈 0. 01. Ultrastructural examination showed mitochondria derangement at LPS 4 h and LPS 24 h groups, including swollen mitochondria with abnormal cristae, and disrupted external membrane of mitochondria. Conclusion Diaphragmatic contractile force-generating capacity decreased remarkably in rats treated with 100 μg/kg LPS,and the diaphragm was susceptible to developing fatigue. These changes may result in respiratory failure.

关 键 词：内毒素类 膈 线粒体 急性肺损伤 

分 类 号：R686[医药卫生—骨科学]